Evidence map›Paper›PMID 29366326›Full record

ArticleACS synthetic biology2018

Detection of a Peptide Biomarker by Engineered Yeast Receptors.

Adebola Adeniran, Sarah Stainbrook, John W Bostick, Keith E J Tyo

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in ACS synthetic biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Rational design of small-molecule responsive protein switches.Protein science : a publication of the Protein Society · 2023
    Review
  5. Pheromone Response and Mating Behavior in Fission Yeast.Microbiology and molecular biology reviews : MMBR · 2022
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Adebola AdeniranDepartment of Chemical and Biological Engineering, ‡Interdisciplinary Biological Sciences Graduate Program, Northwestern University , Evanston, Illinois.ORCID 0000-0002-4906-0907
Sarah StainbrookDepartment of Chemical and Biological Engineering, ‡Interdisciplinary Biological Sciences Graduate Program, Northwestern University , Evanston, Illinois.
John W BostickDepartment of Chemical and Biological Engineering, ‡Interdisciplinary Biological Sciences Graduate Program, Northwestern University , Evanston, Illinois.
Keith E J TyoDepartment of Chemical and Biological Engineering, ‡Interdisciplinary Biological Sciences Graduate Program, Northwestern University , Evanston, Illinois.
Northwestern University · US

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Directed evolution of membrane receptors is challenging as the evolved receptor must not only accommodate a non-native ligand, but also maintain the ability to transduce the detection of the new ligand to any associated intracellular components. The G-protein coupled receptor (GPCR) superfamily is the largest group of membrane receptors. As members of the GPCR family detect a wide range of ligands, GPCRs are an incredibly useful starting point for directed evolution of user-defined analytical tools and diagnostics. The aim of this study was to determine if directed evolution of the yeast Ste2p GPCR, which natively detects the α-factor peptide, could yield a GPCR that detects Cystatin C, a human peptide biomarker. We demonstrate a generalizable approach for evolving Ste2p to detect peptide sequences. Because the target peptide differs significantly from α-factor, a single evolutionary step was infeasible. We turned to a substrate walking approach and evolved receptors for a series of chimeric intermediates with increasing similarity to the biomarker. We validate our previous model as a tool for designing optimal chimeric peptide steps. Finally, we demonstrate the clinical utility of yeast-based biosensors by showing specific activation by a C-terminally amidated Cystatin C peptide in commercially sourced human urine. To our knowledge, this is the first directed evolution of a peptide GPCR.

Indexed as

PeptidesReceptors, Mating FactorSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsBiomarkersCystatin CDirected Molecular EvolutionHumansProtein EngineeringBiomarkersCST3 protein, humanCystatin CPeptidesReceptors, Mating FactorSaccharomyces cerevisiae ProteinsSTE2 protein, S cerevisiaediagnosticsdirected evolutionG-protein coupled receptorsreceptor engineeringsubstrate walking

Identifiers

PMID29366326
PMCPMC5820653
OpenAlexW2784749557

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.